| Project/Area Number |
16K09509
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Asahi University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
金森 寛充 岐阜大学, 医学部附属病院, 講師 (20456502)
岡田 英志 岐阜大学, 医学部附属病院, 講師 (30402176)
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| Research Collaborator |
MATSUO Hitoshi
MIYAZAKI Nagisa
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | エピジェネティクス / クロマチン・リモデリング / DNAメチル化 / 心不全 / 拡張型心筋症 / 心肥大 / 心筋細胞 / 肥大核 / ＤＮＡメチル化 / 超微形態 / 核肥大 |
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| Outline of Final Research Achievements |
Methylated DNA was immunohistochemically detected in human endomyocardial biopsies. DNA methylation was greater in failing heart due to dilated cardiomyopathy (DCM, n=75) than in nonfailing hearts (n=20), of which increase was noted only in cardiomyocytes but not in other cell types. Methylated DNA predominantly localized on nuclear heterochromatin. DNA methylation was significantly correlated with hemodynamic parameters.
We treated 10-week-old delta-sarcoglycan deficient mice, an animal model of DCM, with 5-azacytidine, an inhibitor of DNA methylation at a dose of 1 mg/kg/day. Six weeks later, the survival rate was 100% in the treated mice while it was 69% in the vehicle-treated mice. We are now promoting the animal experiment by incorporating more mice and analyzing the cardiac tissue of the sacrificed mice pathologically and biochemically.
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| Academic Significance and Societal Importance of the Research Achievements |
心筋細胞の肥大した核は従来その機能的意味が不明であったが、エピジェネティク変化ならびに病態との関連を明らかにすることでその意味の重要性を明らかにすることができる。
心不全動物モデルを用いて、エピジェネティック介入（ＤＮＡメチル化阻害薬）により心筋症の病態に変化が見られれば現実的かつ新しい心不全治療法のヒントがえられる可能性がある。
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